Cellular potency, or the potential for a cell to differentiate down various tissue lineages, is the defining characteristic as to the viability of the cell source for a given application. With the establishment of embryonic stem cell lines, the idea of utilizing pluripotent cell sources for regenerative medical applications was introduced as a promising alternative to traditional medical practices. However, there are ethical dilemmas as well as immunological concerns arising from the use of embryonic cell sources in clinical settings. The advent of induced pluripotent stem cells (iPSCs) attempted to circumvent both of these issues and brought the concept of patient-specific pluripotent stem cell attainment to the forefront of the field (Takahashi et al., 2007). This iPSC technology, however, is not without its drawbacks; still in its early stages, the scientific community is trying to decipher the mechanisms underlying the induction of pluripotency (Rezanejad et al., 2012) and overcome the aberrant epigenetic changes arising from the implementation of the technique (Ruiz et al., 2012). Nevertheless, the potential of obtaining pluripotent stem cells from adult tissues is of significant importance and remains as the ultimate goal in overcoming the limitations presently found with other post-natal stem cell populations.
Researchers have worked on the identification and isolation of remnant embryonic-like cells from adult tissues (Conrad et al., 2008; Wagers et al., 2004; Jiang et al., 2002). One of the main focuses has been on tissues arising from the neural crest (Coura et al., 2008; Dupin et al., 2012). Neural crest cells are a population of multipotent and migratory cells that originate from the neural folds during vertebrate development. They are capable of differentiating into diverse cell lineages with regards to the positioning along the anterior-posterior axis (Taneyhill et al., 2008). Beside the specification to cranial ganglia, craniofacial cartilages and bones, thymus, middle ear bones and jaws, the cranial neural crest cells migrating to the pharyngeal pouches and arches can contribute to tooth formation (Degistirici et al., 2008). They give rise to most dental tissues including odontoblasts, dental pulp, apical papilla, dental follicle and periodontal ligament (PDL). PDL is a soft connective tissue located between the root of tooth and alveolar bone socket. It contains a mixed population of fibroblasts, epithelial, undifferentiated mesenchymal, bone and cememtum cells, sitting in the hydrated extracellular ground substance with collagen-rich fibrils. Apart from fixing the tooth to the alveolar bone and withstanding the compressive force during the chewing motion, PDL provides sensory, nutritive and homeostatic support to the alveolar compartment.
Seo and colleagues found that enzymatic treatment of human PDL released a postnatal stem cell population capable of clonogenic growth (Seo et al., 2004). These undifferentiated cells express markers of mesenchymal stem cells (STRO-1, scleraxis), embryonic stem cells (Oct4, Sox2, Nanog and Klf4) and neural crest cells (nestin, Slug, p75 neurotrophin receptor, Sox10), reflecting their pluripotent characteristics, and can differentiate to neurogenic, cardiomyogenic, chondrogenic and osteogenic lineages (Huang et al., 2009; Song et al., 2012; Coura et al., 2008). Given their easy accessibility and vast differentiation potential, PDL-derived stem cells could be an important cell source for regenerative medicine. However, there remains a need in the art for methods of isolating a homogeneous population of pluripotent stem cells from neural crest tissue, like the periodontal ligament, as well as methods of conditioning these pluripotent stem cells to differentiate into desired cell lineages for specific regenerative medicine applications.